Investigations are continuing on superoxide dismutase (SOD), where we have been studying the possible influence of proteolytic enzymes on our measurements. Using phenylmethylsulfonyl fluoride and leupeptin (a specific proteolytic inhibitor of the lysosomal enzyme, cathespin B), we find that most of the age-related decline in SOD activity in mice, reported by other laboratories, can be eliminated. However, the correlation we have found between SOD specific activity per specific metabolic rate and maximum lifespan potential in primate species is not affected by the use of the enzymatic inhibitors. Genetic linkage and functional correlation between the various histocompatibility loci in man and mouse are suggested by mutations in these loci affecting longevity, susceptibility to disease, immunological competence, and levels of SOD, catalase, aryl hydrocarbon hydroxylase, interferon, cAMP and DNA repair. Preliminary evidence indicates that agents known to induce higher levels of SOD (such as paraquat, streptonigrin and dinitrophenol) also reduce the effects of mitomycin C induction of sister chromatin exchange in tissue culture cells and the life-shortening effects of x-rays in mice.